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Physically crosslinked gelatin microgels were functionalized with a bioadhesive molecule, catechol, to study the effect of in situ generated H2O2 on full-thickness wound repair in diabetic mice. Due to the physically crosslinked nature of the microgels, they transition into a hydrogel film upon hydration. The formation of a hydrogel film was confirmed by the changes in their morphology and viscoelastic properties. Additionally, these microgels released up to 86 μM of H2O2 as a result of catechol autoxidation. The generated H2O2 completely eradicated Staphylococcus epidermidis with an initial concentration of 103 CFU mL−1. These microgels were not cytotoxic and promoted VEGF upregulation in immortalized human keratinocytes (HaCaT) in vitro. When the microgels were applied to a full-thickness dermal wound in diabetic mice, dermal wound closure was accelerated over 14 days, achieving a wound closure of 90% based on the wound area. Microgel-treated wounds also resulted in complete re-epithelialization and regeneration of new dermal tissues with morphology and structure resembling those of native tissues. These results indicate that the release of micromolar concentrations of H2O2 can accelerate wound healing in a healing-impaired animal.
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Utilizing Robust Design to Optimize Composite Bioadhesive for Promoting Dermal Wound Repair
Catechol-modified bioadhesives generate hydrogen peroxide (H2O2) during the process of curing. A robust design experiment was utilized to tune the H2O2 release profile and adhesive performance of a catechol-modified polyethylene glycol (PEG) containing silica particles (SiP). An L9 orthogonal array was used to determine the relative contributions of four factors (the PEG architecture, PEG concentration, phosphate-buffered saline (PBS) concentration, and SiP concentration) at three factor levels to the performance of the composite adhesive. The PEG architecture and SiP wt% contributed the most to the variation in the results associated with the H2O2 release profile, as both factors affected the crosslinking of the adhesive matrix and SiP actively degraded the H2O2. The predicted values from this robust design experiment were used to select the adhesive formulations that released 40–80 µM of H2O2 and evaluate their ability to promote wound healing in a full-thickness murine dermal wound model. The treatment with the composite adhesive drastically increased the rate of the wound healing when compared to the untreated controls, while minimizing the epidermal hyperplasia. The release of H2O2 from the catechol and soluble silica from the SiP contributed to the recruitment of keratinocytes to the wound site and effectively promoted the wound healing.
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- Award ID(s):
- 2001076
- PAR ID:
- 10422295
- Date Published:
- Journal Name:
- Polymers
- Volume:
- 15
- Issue:
- 8
- ISSN:
- 2073-4360
- Page Range / eLocation ID:
- 1905
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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Accepted Manuscript1.0
- Journal Article:
- https://doi.org/10.3390/polym15081905
